Our earlier work has established that the difference in behavior of hemoglobins A and S is the result of large differences in the solubilities of their deoxy forms, both in the presence and absence of allosteric effectors. The solubilities of gels and crystals are nearly the same, but the crystals are the less soluble and most reproducible form. The principal new effort will go into completing the solubility studies, with mixtures of a) deoxy S plus other forms of S; and b) deoxy S plus deoxy A, or other forms of A. We will initially continue using our light-scattering or turbidometric apparatus to determine the composition of the resulting crystals or gels and supernatants, and to draw conclusion as to the favored contactor branching points of the constituent molecules. The effect of such additives as IHP, DPG, and substances known to inhibit gelling (e.g., Tris, urea, heavy metals) will also be investigated, with special emphasis on substances known to be capable of penetrating the erythrocyte membrane. The effects of mixing ratios and compositions will be determine not only from solubilities and "minimum gelling concentrations" but also by differences in the thermodynamic parameters of the solubility phenomena. The effects on the kintics of gelling will be continuously monitored on our sensitive low-shear automatic viscometer. If time permits, a limited effort will be devoted to analysis of the differences in the catalytic effects of A and S hemoglobins on a reaction between ascorbate ion and oxygen described in the proposal. We will attempt to estalish conditions for the use of ascorbate as an oxygen scavenger in experiments with deoxyhemoglobin, to avoid the use of dithionite. BIBLIOGRAPHIC REFERENCES: Jones, Maryann McD., Pumphrey, John G., and Steinhardt, Jacinto "A Simple Method for Measring the Solubility of Crystalline Sickle Hemoglobin, Effects of Inositol Hexaphosphate" (1977) Fed. Proc. Vol. 36, No. 3 (ABSTRACT). Kowalczykowski, Steve, and Steinhardt, Jacinto "Kinetics of Hemoglobin S Gelation Followed by Continuously Sensitive Low-Shear Viscometer. Changes in Viscosity and Volume Change of Aggregation" (1977) in J. Mol. Biology , in press.